In this section, you will explore the following question:

  • What are different ways in which translational and post-translational control of gene expression take place?

Connection for AP® Courses

Changing the status of the RNA or the protein itself can affect the amount of protein produced, the function of the protein, or how long the protein resides in the cell. Modifications such as phosphorylation and environmental stimuli can affect the stability and function of the protein.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 4 of the AP® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP®Biology course, an inquiry-based laboratory experience, instructional activities, and AP® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices.

Big Idea 4 Biological systems interact, and these systems and their interactions possess complex properties.
Enduring Understanding 4.A Interactions within biological systems lead to complex properties.
Essential Knowledge 4.A.3 Interactions between external stimuli and regulated gene expression result in specialization of cells, tissues and organs.
Science Practice 1.3 The student can refine representations and models of natural or man-made phenomena and systems in the domain.
Learning Objective 4.7 The student is able to refine representations to illustrate how interactions between external stimuli and gene expression result in specialization of cells, tissues, and organs.

After the RNA has been transported to the cytoplasm, it is translated into protein. Control of this process is largely dependent on the RNA molecule. As previously discussed, the stability of the RNA will have a large impact on its translation into a protein. As the stability changes, the amount of time that it is available for translation also changes.

The Initiation Complex and Translation Rate

Like transcription, translation is controlled by proteins that bind and initiate the process. In translation, the complex that assembles to start the process is referred to as the initiation complex. The first protein to bind to the RNA to initiate translation is the eukaryotic initiation factor-2 (eIF-2). The eIF-2 protein is active when it binds to the high-energy molecule guanosine triphosphate (GTP). GTP provides the energy to start the reaction by giving up a phosphate and becoming guanosine diphosphate (GDP). The eIF-2 protein bound to GTP binds to the small 40S ribosomal subunit. When bound, the methionine initiator tRNA associates with the eIF-2/40S ribosome complex, bringing along with it the mRNA to be translated. At this point, when the initiator complex is assembled, the GTP is converted into GDP and energy is released. The phosphate and the eIF-2 protein are released from the complex and the large 60S ribosomal subunit binds to translate the RNA. The binding of eIF-2 to the RNA is controlled by phosphorylation. If eIF-2 is phosphorylated, it undergoes a conformational change and cannot bind to GTP. Therefore, the initiation complex cannot form properly and translation is impeded (Figure 16.14). When eIF-2 remains unphosphorylated, it binds the RNA and actively translates the protein.


VISUAL CONNECTION

The eIF2 protein is a translation factor that binds to the small 40S ribosome subunit. When eIF2 is phosphorylated, translation is blocked.
Figure 16.14 Gene expression can be controlled by factors that bind the translation initiation complex.
 
An increase in phosphorylation levels of eIF-2 has been observed in patients with neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s. What impact do you think this might have on protein synthesis?
  1. It will increase the rate of translation.
  2. It will not affect the translation process.
  3. It will block the translation of certain proteins.
  4. It will produce multiple fragments of polypeptides.

 Chemical Modifications, Protein Activity, and Longevity

Proteins can be chemically modified with the addition of groups including methyl, phosphate, acetyl, and ubiquitin groups. The addition or removal of these groups from proteins regulates their activity or the length of time they exist in the cell. Sometimes these modifications can regulate where a protein is found in the cell—for example, in the nucleus, the cytoplasm, or attached to the plasma membrane.

Chemical modifications occur in response to external stimuli such as stress, the lack of nutrients, heat, or ultraviolet light exposure. These changes can alter epigenetic accessibility, transcription, mRNA stability, or translation—all resulting in changes in expression of various genes. This is an efficient way for the cell to rapidly change the levels of specific proteins in response to the environment. Because proteins are involved in every stage of gene regulation, the phosphorylation of a protein (depending on the protein that is modified) can alter accessibility to the chromosome, can alter translation (by altering transcription factor binding or function), can change nuclear shuttling (by influencing modifications to the nuclear pore complex), can alter RNA stability (by binding or not binding to the RNA to regulate its stability), can modify translation (increase or decrease), or can change post-translational modifications (add or remove phosphates or other chemical modifications).

The addition of an ubiquitin group to a protein marks that protein for degradation. Ubiquitin acts like a flag indicating that the protein lifespan is complete. These proteins are moved to the proteasome, an organelle that functions to remove proteins, to be degraded (Figure 16.15). One way to control gene expression, therefore, is to alter the longevity of the protein.

Multiple ubiquitin groups bind to a protein. The tagged protein is then fed into the hollow tube of a proteasome. The proteasome degrades the protein.
Figure 16.15  Proteins with ubiquitin tags are marked for degradation within the proteasome.

SCIENCE PRACTICE CONNECTION FOR AP® COURSES

THINK ABOUT IT

How can environmental stimuli such as ultraviolet light exposure or nutrient deficiency modify gene expression?